DESCRIPTION (Investigator's abstract): The aim of this proposal is to hold a series of five annual interdisciplinary conferences on basic and clinical research relevant to fragile X syndrome (FXS). These meetings will be modeled on an initial conference held at the Banbury Conference Center, Cold Spring Harbor Laboratory, and Cold Spring Harbor, NY. The conferences are intended to bring together a broad range of scientists, both those working on FXS and others in allied, relevant fields. Another goal is to introduce young scientists to the area. Fragile X syndrome is the second leading genetic cause of mental retardation. It arises due to expansion of an unstable region of trinucleotide repeats it the 5' untranslated promoter region of the FMR-1 gene, causing hypermethylation of cytosine residues and silencing of the gene. A mouse FMR-l knockout model for the syndrome is available. The function of the fragile X mental retardation protein (FMRP) is not known, but it has recently been shown to be translated al synapses in response to activation of metabotropic receptors by the neurotransmitter glutamate. Relatively subtle phenotypic effects of the disorder are seen in the gross size of several brain regions and in the fine structure of synapses. As the first Banbury Conference indicated (summarized in Sec. C), advances in our knowledge of this disorder are occurring very rapidly. There is no meeting devoted exclusively to basic and clinical research on FXS, and the participants found the first Banbury Conference extremely valuable. It is about proposed that future conferences be organized by a committee of leading researchers and clinicians, with the next meeting focused upon the neural basis of fragile X syndrome.